Blooms and strandings of Chrysaora plocamia are reported to occur along both Atlantic and Pacific South American coasts. First described in Peruvian waters by Lesson (1830) almost two centuries ago as Cyanea plocamia, there is surprisingly little ecological information about this conspicuous animal. This chapter reviews current knowledge about C. plocamia biology and ecology, its relationship with pelagic fisheries and climate and the problems blooms cause in the Humboldt Current and Patagonian shelf ecosystems. Chrysaora plocamia has important ecological roles, including trophic and symbiotic interactions with fish and sea turtles. Population variability has a clear relationship with climate where phases of high C. plocamia biomass were associated with El Niño events occurring during warm “El Viejo” regimes. Interestingly, their estimated biomass occasionally approached those of sardines or anchovies. This large jellyfish negatively affects human industries in the region when abundant, including fisheries, aquaculture, desalination plants and tourism. Understanding relationships between jellyfish blooms and environmental drivers (e.g. ENSO, regime shifts) should allow forecasting of the jellyfish abundance and potential vulnerabilities such that resource managers and industrial fisheries owners may prepare for costly outbreaks.